Aminoglycoside antibiotics have been in use following the isolation of Streptomycin, the first clinically useful aminoglycoside, in 1944. Although the aminoglycosides are particularly useful due to their rapid bactericidal action in infections by susceptible organisms, their use is limited to more severe, complicated infections because of ototoxic and nephrotoxic side-effects. For this reason the aminoglycosides are considered to have a low therapeutic/risk ratio compared to other antibiotics used systemically.
Nephrotoxic effects from aminoglycoside usage are well documented in the literature. A recent description of aminoglycoside adverse reactions and precautions may be found in the 6th Edition of "Drug Evaluations", AMA and W. B. Saunders Co., Philadelphia, PA, pp. 1433-1435 (1986).
Several substances have been reported to be useful in inhibiting aminoglycoside-induced renal damage, particularly amino acid derivatives.
Williams, et al., in U.S. Pat. No. 4,526,888 disclosed the use of certain neutral and anionic polyamino acids to reduce aminoglycoside-induced nephrotoxicity. The specific polyamino acids taught by Williams, et al., are asparagine and aspartic acid polymers.
Meister, et al., in U.S. Pat. No. 4,758,551 reported o-glutamyl amino acids to be nontoxic agents for use in combatting renal toxicity caused by nephrotoxic drugs. Shiokori, et al., in U.S. Pat. No. 4,757,066 disclosed the use of N-acylated amino acids in association with penem or carbapenem antibiotics to reduce renal toxicity caused by use of the antibiotic by itself. In WO 8804-925A (Tulane E. Fund Administration), biosynthetic precursors of oxidizable small peptides such as Glu-Cys or (Gly-Cys-S).sub.2 are among various agents reported to prevent the nephrotoxic effect of aminoglycosides.
Other agents, less related to the present invention, include inter alia D-glucarates (e.g. U.S. Pat. No. 3,928,583, 4,122,171) and amilioride (U.S. Pat. No. 4,654,325).
None of the above-listed substances or references would suggest the polymeric anionic agents of this invention which are not amino acid derivatives or acidic sugar derivatives.